The purpose of the project is to determine the incidence rates, rates of progression, and risk factors for the chronic complications of NIDDM. The study is conducted in the Pima Indians of the Gila River Indian Community, who have participated in a longitudinal epidemiologic study since 1965 (see project Z01 DK 69000). Risk factors for the major complications of diabetes, retinopathy, nephropathy, coronary artery disease, and peripheral vascular disease are determined by longitudinal followup of diabetic subjects. Methods of ascertainment of these complications include fundus photography, measurement of urine albumin and serum creatinine concentrations, electrocardiography, and documentation of lower extremity amputations. These complications are responsible for the major morbidity and excessive mortality associated with diabetes in this population. The incidence rates of severe complications such as end stage renal disease, cataract requiring surgical treatment, and lower extremity amputations are as high among diabetic Pimas as reported anywhere else in the world. Diabetic nephropathy is the leading cause of deaths among diabetic Pimas. Late stages of nephropathy can be predicted by minor abnormalities of urinary albumin excretion early in the course of the disease and show strong familial aggregation suggesting a genetic susceptibility to nephropathy as well as to diabetes. Development of nephropathy is predicted by elevated blood pressure before the onset of diabetes, suggesting that predisposition to diabetic renal disease is determined, in part, even before the onset of diabetes.